1. Technical Field
This invention relates to novel anthracycline compounds and uses thereof. More particularly, the invention relates to 3'-deamino-3'-(4-morpholinyl) derivatives of 13-deoxocarminomycin (hereinafter referred to as "R20X") and 10-hydroxy-13-deoxocarminomycin (hereinafter referred to as "R20X2", R20X and R20X2 being referred to collectively as "R20 substances") which are anthracycline compounds having antitumor activity and to a 3'-deamino-3'-(4-morpholinyl) derivative of 11-deoxy-13-deoxocarminomycin (hereinafter referred to as "R20Y5") which is also an anthracycline compound having antitumor activity.
2. Prior Art
Anthracycline compounds heretofore known are, for example, daunomycin (U.S. Pat. No. 3,616,242) and adriamycin (U.S. Pat. No. 3,590,028) obtained from the culture broths of actinomycetes, and these compounds are widely used for clinical purposes as antitumor agents. They, however, are not satisfactorily acceptable pharmaceutical agents since they cause strong side effects while exhibiting remarkable antitumor activity.
As a compound relevant to the 3'-deamino-3'-(4-morpholinyl) derivatives of the present invention, Rivola, G. et al. obtained R20X which is a leading compound of the derivatives from the culture broth of Streptomyces peucetius var. carminatus (DSM 1524, ATCC 31502, FRI 4929, Farmitalia Carlo Erba collection of microorganisms No. DR 81 F.I.) and have reported that the compound has antitumor activity (West German Patent Application Laid-Open Pub. No. 3,012,665). Giuseppe Cassinelli et al. also obtained R20Y5 which is another leading compound of the above derivatives from the culture broth of a mutant strain of Streptomyces peucetius var. caecius, i.e., Streptomyces peucetius var. aureus and have reported that this compound has antitumor activity (Japanese Patent Application Laid-Open Pub. No. 76896/1980).
Further, various derivatives of adriamycin, daunomycin and carminomycin were synthesized as morpholinyl derivatives of anthracycline compounds and have been reported to have antitumor activity (Japanese Patent Application Laid-Open Pub. No. 163393/1982; U.S. Pat. No. 4,301,277; Japanese Patent Application Laid-Open Pub. No. 212484/1984; Japanese Patent Application Laid-Open Pub. No. 212499/1984; Mosher, C. W. et al., J. Med. Chem. 25 pp. 18-24 (1982); Johnston, J. B., Biochemical Pharmacology 32(21) pp. 3255-3258 (1983); Acton, E. M., J. Med. Chem. 27 pp. 638-645 (1984)).
As far as we are aware, however, these compounds are not again necessarily acceptable on the point of high antitumor activity or low toxicity.
Anthracycline compounds form a group of useful antitumor agents, so that there has been constant demand for better anthracycline compounds.